Chemotherapy Could Make a Comeback, But Only Clinical Trials Will Tell

Immunotherapy has been a hot topic in the bladder cancer space, with five Food and Drug Administration (FDA) approvals in 2017 alone. But patients and physicians should not discredit chemotherapy, which may be making a comeback to help improve outcomes in these patients, according to Parminder Singh, M.D.

“Chemotherapy is going to make a comeback as a sensitizing agent for the immune system and consequent immune therapy,” Singh, a hematologist/oncologists at the Mayo Clinic in Phoenix, Arizona, said in an interview with OncLive, a sister publication of CURE.

Current FDA-approved immunotherapy regimens for the treatment of bladder cancer include Keytruda (pembrolizumab) and Tecentriq (atezolizumab) in the first- and second-line setting, and Imfinzi (durvalumab), Opdivo (nivolumab) and Bavencio (avelumab) for cisplatin-ineligible patients who progressed on platinum-based chemotherapy.

Only about 1 in 7 patients derive benefit from these drugs when they are given by themselves. However, Singh suggested that adding chemotherapy to a PD-1 or PD-L1 inhibitor might boost response rates, as it has in other settings, such as lung cancer.

“It seems counterintuitive because chemotherapy is considered immune-suppressive, but it appears that chemotherapy can make the tumor environment ‘hot’ so that it responds to and is controlled by immunotherapy stimulus,” he added.

Chemotherapy can aid in making a tumor “hot” — meaning that it attracts tumor-infiltrating lymphocytes (TILs), which are linked to killing tumor cells – priming it to respond better to immunotherapy treatment.

It is important to remember that although chemotherapy response rates are higher, there are select patient populations that derive the greatest benefit from immunotherapy. For example, if a patient progresses on cisplatin-based chemotherapy, they face limited options, for which immunotherapy then comes in to play. In addition, immunotherapy is also frequently used as a firstline option for elderly patients who may not be good candidates for platinum-based chemotherapy.

“Immune therapy doesn’t work for everyone, but at the same time, it provides an option that is well-tolerated,” Singh said.

Researchers hope that clinical trials will work to increase the number of patients who response to immunotherapy treatment. Therefore, a variety of trials are being conducted to evaluate treatment regimens using two immunotherapy agents or in combination with chemotherapy and/or radiation.

“All of these trials will shed light on the activity of combining different modalities,” Singh said.

As new agents and combinations come down the pipeline, Singh emphasized the importance of clinical trial enrollment. In particular, this mean breaking down misconceptions that some patients have about trials, such as ending up in a placebo group and not receiving the experimental drug at all.

While that may be true in some situations, patients do have options when it comes to clinical trial enrollment.

“Though a patient may feel that they’re going into an experiment where they may or may not receive study medication, there are also early-phase trials — ones that are looking for safety and for signals of efficacy, in which all patients receive the study medication,” Singh said. “If their conscience doesn’t allow them to go on a phase 3 randomized trial, early-phase trials are an option to get access to new agents that are not available on the market.”

After years without any advances in the bladder cancer space, it was the patients on clinical trials that moved the field forward, and led to last year being a landmark year in terms of approvals for bladder cancer. With higher participation in clinical trials, more advances can be made, Singh added. “A patient’s contribution is invaluable, and we need to understand and appreciate that, so they can continue to support our efforts.”